The Transfusion Medicine and Hemostasis (TMH) Clinical Trials Network was formed in 2002 in response to a demonstrated need for clinical trials in the use of transfusion therapy and the management of hemostatic disorders. Although blood product use continues to increase, the lack of prospective clinical trials limits our ability to provide clear guidelines for the use of these limited resources. In contrast, many hemostatic disorders, such as thrombotic thrombocytopenic purpura (TTP) and hemophilia A patients with inhibitors, are relatively rare, making it difficult to answer important clinical questions due to a lack of sufficient numbers of patients at a single institution. The TMH Network currently has clinical trials recruiting patients to determine the optimal platelet transfusion dose and define the role of fresh frozen plasma in patients with prolonged clotting times undergoing liver biopsy, and trials are close to initiation looking at patients with hemophilia and inhibitors, TTP, and heparin-induced thrombocytopenia. Building on the progress to date, we propose to continue our commitment at Duke to the TMH Network by working on the following Specific Aims: (1) Maintain, and further enhance, as needed, a structure to support the development, implementation and conduct of clinical trials in the areas of transfusion medicine and hemostasis. This will be done in collaboration with the New England Research Institutes as Data Coordinating Center, and program staff at NHLBI; (2) Utilizing this structure of working and study oversight subcommittees, complete ongoing trials and develop, refine and complete new trials proposed in this application; (3) Develop collaborative relationships and support training opportunities to facilitate the success of the proposed clinical trials and further the fields of transfusion medicine and hemostasis; and (4) Disseminate results of the TMH Clinical Trials Network through presentation and publication of clinical trial results and other TMH Network activities. This network will complete clinical research studies that answer important questions concerning the best way to use platelets, plasma, and other blood products in patients at risk of bleeding. This network is also studying treatment approaches for patients with rare bleeding disorders such as hemophilia. These studies are not possible at single institutions and require the multicenter approach of the Transfusion Medicine and Hemostasis Clinical Trials Network.